December will be a big month for Achillion's complement inhibitor and Aquestive's ALS hopes.

Welcome to your weekly digest of approaching regulatory and clinical readouts. The sector will see in December whether Achillion Pharmaceutical’s transformation from hepatitis C aspirant to rare disease specialist was successful as interim data from four trials of complement factor D inhibitor ACHN-4471 emerge.

The small molecule is being tested in paroxysmal nocturnal haemoglobinuria (PNH), as a monotherapy and added to Soliris, as well as in C3 glomerulopathy (C3G). In the PNH monotherapy trial, the project must reduce levels of serum lactate dehydrogenase, a marker of uncontrolled complement activation, when compared with baseline measurements. In the Soliris combination trial, researchers will be hoping to see a rise in blood haemoglobin levels – patients will be randomised to four different doses of ACH-4471, only one of which is defined as “optimal”, hoping to show a greater improvement in haemoglobin levels over patients in the “non-optimal” dosing groups.

In C3G, a condition in which immune system dysfunction causes damage to the kidneys, Achillion will hope that renal biopsies of patients in the trial show a reduction in the amount of the protein C3 after 12 months of treatment. Leerink analyst Joseph Schwartz described this trial as “needle-moving for the stock”. He wrote: “C3G is a rare kidney disease with no approved treatment, whereby ACHN could emerge as a leader among the handful of competitors vying for first-to-market status”.

Indeed, several projects are in mid-stage development for the condition, including Vifor’s avacopan and Johnson & Johnson and Genmab’s Darzalex (see table).

Mid-stage projects in C3 glomerulopathy

Avacopan

Vifor

Darzalex

J&J/Genmab

OMS721

Omeros

APL-2

Apellis

Source: EvaluatePharma.

Achillion has a market capitalisation of $403m. ACHN-4471 has a net present value of $100m, as calculated from EvaluatePharma’s consensus of sellside analysts, and the company had $283m at September 30. Thus, success at phase II is almost certain to lead to a substantial share uplift as investors raise forecasts and anticipate dealmaking talks.

Aquestive has not had the smoothest of rides since it made its stock market debut in July. The high of getting first temporary and then full approval for Sympazan, its oral film product to treat seizures associated with Lennox-Gastaut syndrome, has been tempered by the FDA slapping its oral film form of tadalafil for erectile dysfunction with a complete response letter.

Adding to the misery was partner Indivior losing a court ruling against generics company Dr Reddy’s, which allowed the Indian generics company to begin selling a generic version of Indivior’s Suboxone. Suboxone is a sublingual treatment for opioid overdose that uses Aquestive’s proprietary PharmaFilm technology.

Good news would be welcomed by shareholders, who have seen the stock dip from its launch price of $15 to just $8.72 this week.

Fingers crossed

The next opportunity to offer some comfort to those who might still be in stock lock-ins from the summer IPO will be the phase III trial results from a swallowing study of AQST-177, the group’s treatment for amyotrophic lateral sclerosis (ALS). The full data are due by the end of the year and if positive Aquestive is hoping to file the drug with the FDA in the first quarter.

Some encouragement for a positive outcome might have been given with the decision of the FDA to end the swallowing test early based on interim data analysis earlier this month. However, ALS is a notoriously intractable disease and it is hard to see how Aquestive might succeed with what is essentially a reformulation of Sanofi’s now generic Rilutek, given that others such as Cytokine and Astellas’s Tirasemtiv have failed.

Such is the difficulty with ALS that very few late stage drugs actually have analysts sales forecasts attached to them.

Aquestive obviously sees an opportunity in this market. However, given its recent history of disappointments, it might have picked one of the industry’s riskiest areas for its next stock catalyst.